Recent developments in elastography suggest it is possible to image linear and nonlinear elastic parameters of breast tissues as well as shear wave propagation velocity and strains, and these parameters might be useful in non-invasively differentiating benign tumors from breast cancers. However, some commercial elastographic systems have not lived up to their high expectations. Our objectives of this proposal are twofold: 1) to build a virtual breast ultrasound simulation platform to accelerate development of UEI systems; and 2) to investigate mechanistic links between tissue microstructure and corresponding macroscopic mechanical properties of the tissue by using this novel ultrasound simulation infrastructure. The immediate outcome of this research includes a virtual open source software infrastructure for multi-scale biomechanical modeling of female breasts and subsequent ultrasound simulations. In addition to exposing undergraduate students to advanced cancer imaging research, impacts of this research include: 1)improving our understanding of resolution and contrast limits of elastographic systems in a complex but controllable virtual environment; and 2)enhancing our capability to infer micro-structural changes of ECM under image guidance. The latter will open new avenues for breast cancer diagnosis and therapy. Preliminary data demonstrate our research methodology is feasible. This AREA award will provide the Michigan Tech team with resources to train undergraduate and graduate students, obtain data for future NIH funding, and build a sustainable undergraduate research program in breast cancer imaging.